Immunization, Vaccines and Biologicals

Tuberculosis vaccines

Tuberculosis development

To win the fight against tuberculosis (TB), a comprehensive approach is needed that includes new and more effective vaccines as well as improved diagnostics and treatment. The Bacille Calmette-Guérin (BCG) vaccine developed in 1921 remains the only vaccine against TB. Unfortunately, it is only partially effective: it provides some protection against severe forms of pediatric TB, but is unreliable against adult pulmonary TB, which accounts for most of the disease burden worldwide. Although BCG is the most widely administered vaccine in the world, the number of TB cases have never been higher. There is therefore an urgent need for a new, safe and effective vaccine that prevents all forms of TB, including drug-resistant strains, in all age groups and in people with HIV.

Multiple approaches to TB vaccine development

Due to the complex nature of Mycobacterium tuberculosis (Mtb) and its interaction with human hosts, scientists are examining multiple approaches for new TB vaccines, as described below.

  • Priming TB vaccines are intended for use in newborns to replace BCG, and to prevent TB in people who have not been infected with Mtb.
  • "Early" booster TB vaccines are delivered together with other childhood vaccines in early infancy to amplify the immune repose induced by the priming vaccine.
  • "Late" booster TB vaccines are administered post-infancy, typically to schoolchildren, adolescents or adults who are potentially infected, but show no symptoms of disease. These vaccines are intended to reduce progression from latent to active disease.
  • Therapeutic vaccines are given to individuals with active TB in conjunction with TB drug therapy with the aim of shortening the duration of the therapy or reducing relapses after completion of treatment.

Current state-of-the-art

By the end of 2010, 12 TB vaccine candidates had entered clinical trials. Phase I clinical trials largely determine the safety of a vaccine, the optimal dosage, and initiate age de-escalation studies, i.e. from the healthy adult towards the desired target age group. Phase II evaluation then focuses primarily on immunogenicity.

Currently, two adjuvanted protein subunit vaccines, so-called fusion proteins, are in Phase IIa trials. In parallel, the two most advanced vaccine candidates in terms of their clinical evaluation are in Phase IIb Test-of-Concept (ToC) trials, i.e. clinical trials that provide a preliminary estimate of protection.

Both are virus vectored vaccines expressing one or more TB antigens:

  • Aeras 402, based on the adenovirus 35 virus vector expressing several TB antigens.
  • MVA-85A, based on the "modified vaccinia Ankara" vector and expresses TB antigen 85A.

Clearly, the availability of a new TB vaccine depends on a multitude of factors, but most importantly on its efficacy. Assuming that one of the most advanced vaccine candidates shows sufficient efficacy, the first new TB vaccine in a 100 years could become available around 2018.